This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A key problem in biology is assigning function to proteins of known sequence, sometimes even known structures, but unknown activity. Examples include efforts to de-orphan receptors, determine targets in cell-based (functional) screens, and structural genomics. Much effort has been focused on bioinformatics tools, but a possible role for chemical information has largely been ignored. Many proteins recognize characteristic sets of organic molecules (ligands), either in their normal function or as reagents that interrupt this function. We propose to "fingerprint" proteins using their ligands. Based on the similarity of this fingerprint to those of other proteins, it should be possible to create ligand chemistry-based linkage maps and to infer protein function.